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OBJECTIVE: To determine if extremely low birth weight infants with surgical necrotizing enterocolitis have a higher risk of death or neurodevelopmental impairment and neurodevelopmental impairment among survivors (secondary outcome) at 18-22 months corrected age compared with infants with spontaneous intestinal perforation and infants without necrotizing enterocolitis or spontaneous intestinal perforation. STUDY DESIGN: Retrospective analysis of the Neonatal Research Network very low birth weight registry, evaluating extremely low birth weight infants born between 2000 and 2005. The study infants were designated into three groups: (1) spontaneous intestinal perforation without necrotizing enterocolitis; (2) surgical necrotizing enterocolitis (Bell's stage III); and (3) neither spontaneous intestinal perforation nor necrotizing enterocolitis. Multivariate logistic regression analysis was performed to evaluate the association between the clinical group and death or neurodevelopmental impairment, controlling for multiple confounding factors including center.RESULT: Infants with surgical necrotizing enterocolitis had the highest rate of death before hospital discharge (53.5%) and death or neurodevelopmental impairment (82.3%) compared with infants in the spontaneous intestinal perforation group (39.1 and 79.3%) and no necrotizing enterocolitis/no spontaneous intestinal perforation group (22.1 and 53.3%; P<0.001). Similar results were observed for neurodevelopmental impairment among survivors. On logistic regression analysis, both spontaneous intestinal perforation and surgical necrotizing enterocolitis were associated with increased risk of death or neurodevelopmental impairment (adjusted odds ratio 2.21, 95% confidence interval (CI): 1.5, 3.2 and adjusted OR 2.11, 95% CI: 1.5, 2.9, respectively) and neurodevelopmental impairment among survivors (adjusted OR 2.17, 95% CI: 1.4, 3.2 and adjusted OR 1.70, 95% CI: 1.2, 2.4, respectively). CONCLUSION: Spontaneous intestinal perforation and surgical necrotizing enterocolitis are associated with a similar increase in the risk of death or neurodevelopmental impairment and neurodevelopmental impairment among extremely low birth weight survivors at 18-22 months corrected age. [ABSTRACT FROM AUTHOR]

Critically ill babies, especially if preterm and requiring neonatal intensive care, are at risk of oesophageal and gastric lesions which may result in acute gastric bleeding. The pathophysiology of these stress-induced lesions is not always clear, but one of the influencing factors is a low gastric pH. Maintaining the gastric pH above 4 is recommended to minimise morbidity from such lesions. The aim of this study was to compare pH sensitive litmus paper/stick measurements in this population against the gold standard, intragastric pH readings. Gastric juice was collected four hourly and tested with Panpeha(R) multicolour sensitive litmus paper. This result was compared with simultaneous pH probe/meter measurements.The study comprised of 62 babies, ranging in gestation from 24 to 41 weeks (median=30; mean=31; SD=4.331) and a birth weight range from 540-3655 grams (median=1391; mean=1641; SD=806); 261 paired readings were analysed. The measurements of gastric pH obtained by pH sensitive litmus paper were consistently 0.5pH units below the measurements obtained by the 'gold standard', an intragastric probe. If a gastric pH<4 was to be taken as a treatment criterion, 25% of the infants would have received inappropriate treatment based on the results of pH sensitive litmus paper readings. In conclusion, this technique for cotside estimation of gastric pH is poor. This has implications when using measurements from pH sensitive indicator strips to initiate or monitor treatments aimed at preventing the development of neonatal stress-induced gastric ulcers or to assess that feeding tubes are correctly positioned in the stomach. [ABSTRACT FROM AUTHOR]

Background: High-dose erythropoietin has been shown to have a neuroprotective effect in preclinical models of neonatal brain injury, and phase 2 trials have suggested possible efficacy; however, the benefits and safety of this therapy in extremely preterm infants have not been established.Methods: In this multicenter, randomized, double-blind trial of high-dose erythropoietin, we assigned 941 infants who were born at 24 weeks 0 days to 27 weeks 6 days of gestation to receive erythropoietin or placebo within 24 hours after birth. Erythropoietin was administered intravenously at a dose of 1000 U per kilogram of body weight every 48 hours for a total of six doses, followed by a maintenance dose of 400 U per kilogram three times per week by subcutaneous injection through 32 completed weeks of postmenstrual age. Placebo was administered as intravenous saline followed by sham injections. The primary outcome was death or severe neurodevelopmental impairment at 22 to 26 months of postmenstrual age. Severe neurodevelopmental impairment was defined as severe cerebral palsy or a composite motor or composite cognitive score of less than 70 (which corresponds to 2 SD below the mean, with higher scores indicating better performance) on the Bayley Scales of Infant and Toddler Development, third edition.Results: A total of 741 infants were included in the per-protocol efficacy analysis: 376 received erythropoietin and 365 received placebo. There was no significant difference between the erythropoietin group and the placebo group in the incidence of death or severe neurodevelopmental impairment at 2 years of age (97 children [26%] vs. 94 children [26%]; relative risk, 1.03; 95% confidence interval, 0.81 to 1.32; P = 0.80). There were no significant differences between the groups in the rates of retinopathy of prematurity, intracranial hemorrhage, sepsis, necrotizing enterocolitis, bronchopulmonary dysplasia, or death or in the frequency of serious adverse events.Conclusions: High-dose erythropoietin treatment administered to extremely preterm infants from 24 hours after birth through 32 weeks of postmenstrual age did not result in a lower risk of severe neurodevelopmental impairment or death at 2 years of age. (Funded by the National Institute of Neurological Disorders and Stroke; PENUT ClinicalTrials.gov number, NCT01378273.). [ABSTRACT FROM AUTHOR]

Abstract Background In the post-genomic era, multi-faceted research on complex disorders such as autism has generated diverse types of molecular information related to its pathogenesis. The rapid accumulation of putative candidate genes/loci for Autism Spectrum Disorders (ASD) and ASD-related animal models poses a major challenge for systematic analysis of their content. We previously created the Autism Database (AutDB) to provide a publicly available web portal for ongoing collection, manual annotation, and visualization of genes linked to ASD. Here, we describe the design, development, and integration of a new module within AutDB for ongoing collection and comprehensive cataloguing of ASD-related animal models. Description As with the original AutDB, all data is extracted from published, peer-reviewed scientific literature. Animal models are annotated with a new standardized vocabulary of phenotypic terms developed by our researchers which is designed to reflect the diverse clinical manifestations of ASD. The new Animal Model module is seamlessly integrated to AutDB for dissemination of diverse information related to ASD. Animal model entries within the new module are linked to corresponding candidate genes in the original "Human Gene" module of the resource, thereby allowing for cross-modal navigation between gene models and human gene studies. Although the current release of the Animal Model module is restricted to mouse models, it was designed with an expandable framework which can easily incorporate additional species and non-genetic etiological models of autism in the future. Conclusions Importantly, this modular ASD database provides a platform from which data mining, bioinformatics, and/or computational biology strategies may be adopted to develop predictive disease models that may offer further insights into the molecular underpinnings of this disorder. It also serves as a general model for disease-driven databases curating phenotypic characteristics of corresponding animal models.

Objective: To study the effects of playing mother's recorded voice to preterm infants in the NICU on their mothers' mental health as measured by the Depression, Anxiety and Stress Scale -21 (DASS-21) questionnaire., Design/methods: This was a pilot single center prospective randomized controlled trial done at a level IV NICU. The trial was registered at clinicaltrials.gov (NCT04559620). Inclusion criteria were mothers of preterm infants with gestational ages between 26wks and 30 weeks. DASS-21 questionnaire was administered to all the enrolled mothers in the first week after birth followed by recording of their voice by the music therapists. In the interventional group, recorded maternal voice was played into the infant incubator between 15 and 21 days of life. A second DASS-21 was administered between 21 and 23 days of life. The Wilcoxon rank-sum test was used to compare DASS-21 scores between the two groups and Wilcoxon signed-rank test was used to compare the pre- and post-intervention DASS-21 scores., Results: Forty eligible mothers were randomized: 20 to the intervention group and 20 to the control group. The baseline maternal and neonatal characteristics were similar between the two groups. There was no significant difference in the DASS-21 scores between the two groups at baseline or after the study intervention. There was no difference in the pre- and post-interventional DASS-21 scores or its individual components in the experimental group. There was a significant decrease in the total DASS-21 score and the anxiety component of DASS-21 between weeks 1 and 4 in the control group., Conclusion: In this pilot randomized control study, recorded maternal voice played into preterm infant's incubator did not have any effect on maternal mental health as measured by the DASS-21 questionnaire. Data obtained in this pilot study are useful in future RCTs (Randomized Controlled Trial) to address this important issue.

Background: The purpose of this study was to assess the impact of metabolic and bariatric surgery (MBS) on Quality of Life (QoL) in Indian patients with obesity over 10 years., Methods: A retrospective chart review was conducted at 11 centres for individuals with MBS between February 2013 and May 2022. Patient medical records provided the source of de-identified data., Results: Data from 2132 individuals with a mean age of 43.28 ± 11.96 years was analysed. There were 37.43% men and 62.57% females in the study population. The study population had a mean preoperative body mass index (BMI) of 45.71 ± 10.38 kg/m 2 . The Bariatric Analysis and Reporting Outcome System (BAROS) scoring method showed a higher overall QoL score throughout all follow-up periods, with 'very good' outcomes at one, three and 7 years and 'good' outcomes at 5 and 10 years. Improvements in QoL were associated with a substantial improvement (p < .01) in BMI at every follow-up time point., Conclusions: Following MBS, individuals with obesity exhibited a substantial and long-term improvement in their overall QoL for up to 10 years. This study presents Indian data on QoL, which is considered one of the most important decision-making factors for or against an intervention., (© 2024 The Author(s). Clinical Obesity published by John Wiley & Sons Ltd on behalf of World Obesity Federation.)

Introduction: Complicated femoral hernias can be managed by minimally invasive surgery techniques in the select group of patients. This helps reduce the morbidity of open surgery and enables faster recovery of the patient., Concerns Addressed: Delay in diagnosis can be reduced by a good clinical examination of the patient with a high index of suspicion for these patients. Imaging helps to confirm the clinical diagnosis and plan the operative intervention. In trained hands, the complicated femoral hernias can be managed by laparoscopy which enables better visualisation. Post-operative recovery is also enabled by the minimally invasive surgery done., Conclusion: Minimally invasive laparoscopic surgery can be done in the select group of cases of complicated femoral hernia by trained surgeons.

Introduction: Accidental ingestion of dentures can lead to certain life-threatening complications. Duodenal impaction is particularly a challenging situation. Minimally invasive procedures can help when done as a combined approach., Our Modification: Endoscopy is the first-line management of retained foreign bodies. However, in difficult locations, a combined endoscopy and laparoscopy can help prevent complications and associated morbidity and improve outcome for the patient., Benefit: Decreased post-operative morbidity and better outcome for the patient., Competing Interests: None

Background: Although safe practice guidelines were issued by the Obesity and Metabolic Surgery Society of India (OSSI) in the end of May 2020, surgeons have been in a dilemma about risk of subjecting patients to hospitalisation and bariatric surgery. This survey was conducted with the objective to evaluate the risk of coronavirus disease-19 (COVID-19) infection in peri- and post-operative period after bariatric and metabolic surgery (BMS)., Methods: A survey with OSSI members was conducted from 20 July 2020 to 31 August 2020 in accordance with EQUATOR guidelines. Google Form was circulated to all surgeon members through E-mail and WhatsApp TM . In the second phase, clinical details were captured from surgeons who reported positive cases., Results: One thousand three hundred and seven BMS were reported from 1 January 2020 to 15 July 2020. Seventy-eight per cent were performed prior to 31 March 2020 and 276 were performed after 1 April 2020. Of these, 13 (0.99%) patients were reported positive for COVID-19 in the post-operative period. All suffered from a mild disease and there was no mortality. Eighty-seven positive cases were reported from patients who underwent BMS prior to 31 December 2019. Of these, 82.7% of patients had mild disease, 13.7% of patients had moderate symptoms and four patients succumbed to COVID-19., Conclusion: BMS may be considered as a safe treatment option for patients suffering from clinically severe obesity during the COVID-19 pandemic. Due care must be taken to protect patients and healthcare workers and all procedures must be conducted in line with the safe practice guidelines., Competing Interests: None

Background: The pathogenesis of BPD includes inflammation and oxidative stress in the immature lung. Corticosteroids improve respiratory status and outcome, but the optimal treatment regimen for benefit with low systemic effects is uncertain., Methods: In a pilot dose escalation trial, we administered ≤5 daily doses of budesonide in surfactant to 24 intubated premature infants (Steroid And Surfactant in ELGANs (SASSIE)). Untargeted metabolomics was performed on dried blood spots using UPLC-MS/MS. Tracheal aspirate IL-8 concentration was determined as a measure of lung inflammation., Results: Metabolomics data for 829 biochemicals were obtained on 121 blood samples over 96 h from 23 infants receiving 0.025, 0.05, or 0.1 mg budesonide/kg. Ninety metabolites were increased or decreased in a time- and dose-dependent manner at q ≤ 0.1 with overrepresentation in lipid and amino acid super pathways. Different dose response patterns occurred, with negative regulation associated with highest sensitivity to budesonide. Baseline levels of 22 regulated biochemicals correlated with lung inflammation (IL-8), with highest significance for sphingosine and thiamin., Conclusions: Numerous metabolic pathways are regulated in a dose-dependent manner by glucocorticoids, which apparently act via distinct mechanisms that impact dose sensitivity. The findings identify candidate blood biochemicals as biomarkers of lung inflammation and systemic responses to corticosteroids., Impact: Treatment of premature infants in respiratory failure with 0.1 mg/kg intra-tracheal budesonide in surfactant alters levels of ~11% of detected blood biochemicals in discrete time- and dose-dependent patterns. A subset of glucocorticoid-regulated biochemicals is associated with lung inflammatory status as assessed by lung fluid cytokine concentration. Lower doses of budesonide in surfactant than currently used may provide adequate anti-inflammatory responses in the lung with fewer systemic effects, improving the benefit:risk ratio., (© 2021. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Background: There are data on the safety of cancer surgery and the efficacy of preventive strategies on the prevention of postoperative symptomatic COVID-19 in these patients. But there is little such data for any elective surgery. The main objectives of this study were to examine the safety of bariatric surgery (BS) during the coronavirus disease 2019 (COVID-19) pandemic and to determine the efficacy of perioperative COVID-19 protective strategies on postoperative symptomatic COVID-19 rates., Methods: We conducted an international cohort study to determine all-cause and COVID-19-specific 30-day morbidity and mortality of BS performed between 01/05/2020 and 31/10/2020., Results: Four hundred ninety-nine surgeons from 185 centres in 42 countries provided data on 7704 patients. Elective primary BS (n = 7084) was associated with a 30-day morbidity of 6.76% (n = 479) and a 30-day mortality of 0.14% (n = 10). Emergency BS, revisional BS, insulin-treated type 2 diabetes, and untreated obstructive sleep apnoea were associated with increased complications on multivariable analysis. Forty-three patients developed symptomatic COVID-19 postoperatively, with a higher risk in non-whites. Preoperative self-isolation, preoperative testing for SARS-CoV-2, and surgery in institutions not concurrently treating COVID-19 patients did not reduce the incidence of postoperative COVID-19. Postoperative symptomatic COVID-19 was more likely if the surgery was performed during a COVID-19 peak in that country., Conclusions: BS can be performed safely during the COVID-19 pandemic with appropriate perioperative protocols. There was no relationship between preoperative testing for COVID-19 and self-isolation with symptomatic postoperative COVID-19. The risk of postoperative COVID-19 risk was greater in non-whites or if BS was performed during a local peak., (© 2021. The Author(s).)

Background: Complications after bariatric surgery are not uncommon occurrences that influence the choice of operations both by patients and by surgeons. Complications may be classified as intra-operative, early (<30 days post-operatively) or late (beyond 30 days). The prevalence of complications is influenced by the sample size, surgeon's experience and length and percentage of follow-up. There are no multicentric reports of post-bariatric complications from India., Objectives: To examine the various complications after different bariatric operations that currently performed in India., Materials and Methods: A scientific committee designed a questionnaire to examine the post-bariatric surgery complications during a fixed time period in India. Data requested included demographic data, co-morbidities, type of procedure, complications, investigations and management of complications. This questionnaire was sent to all centres where bariatric surgery is performed in India. Data collected were reviewed, were analysed and are presented., Results: Twenty-four centres responded with a report on 11,568 bariatric procedures. These included 4776 (41.3%) sleeve gastrectomy (SG), 3187 (27.5%) one anastomosis gastric bypass (OAGB), 2993 (25.9%) Roux-en-Y gastric bypass (RYGB) and 612 (5.3%) other procedures. Total reported complications were 363 (3.13%). Post-operative bleeding (0.75%) and nutritional deficiency (0.75%) were the two most common complications. Leaks (P = 0.009) and gastro-oesophageal reflux disease (P = 0.019) were significantly higher in SG, marginal ulcers in OAGB (P = 0.000), intestinal obstruction in RYGB (P = 0.001) and nutritional complications in other procedures (P = 0.000). Overall, the percentage of complications was higher in 'other' procedures (6.05%, P = 0.000). There were 18 (0.16%) reported mortalities., Conclusions: The post-bariatric composite complication rate from the 24 participating centres in this study from India is at par with the published data. Aggressive post-bariatric follow-up is required to improve nutritional outcomes., Competing Interests: None

The American Academy of Pediatrics (AAP) Committee on Infectious Diseases (COID) periodically publishes recommendations for respiratory syncytial virus (RSV) immunoprophylaxis (IP) use in pediatric patients considered to be at highest risk for severe RSV infection. In 2014, for the first time, the AAP COID stopped recommending the use of RSV IP for otherwise healthy infants born at 29 weeks' gestational age (wGA) or later, stating that RSV hospitalization (RSVH) rates in this population are similar to those of term infants. Subsequently, epidemiological studies in the US at national and regional levels provided evidence of the impact of the policy change in 29-34 wGA infants. The results of these studies demonstrated a significant decrease in IP use after 2014 that was associated with an increased rate of RSVH in 29-34 wGA infants and an increase in morbidities. RSVH-related morbidities included pediatric intensive care unit (ICU) admissions, an increased need for mechanical ventilation, and an increase in the length of stay. After the change in recommendations, the costs of RSVH also rose among 29-34 wGA infants. The severity of the illness and expenses associated with RSVH were generally higher among 29-34 wGA infants of younger chronologic age compared with older preterm infants. Overall, these studies underscore that 29-34 wGA infants continue to be a high-risk pediatric population that could benefit from the protection provided by RSV IP. On the basis of these data, in 2018, the National Perinatal Association developed guidelines that recommended RSV IP for all ≤ 32 wGA infants and 32-35 wGA infants with additional risk factors. Re-evaluation of the AAP COID policy is warranted in light of these observations.

Bariatric and metabolic surgery (BMS), the only effective option for patients with obesity with or without comorbidities, has been stopped temporarily due to the ongoing novel corona virus disease (COVID-19) pandemic. However, there has been a recent change in the governmental strategy of dealing with this virus from 'Stay at Home' to 'Stay Alert' in many countries including India. A host of health services including elective surgeries are being resumed. In view of the possibility of resumption of BMS in near future, Obesity and Metabolic Surgery Society of India (OSSI) constituted a committee of experienced surgeons to give recommendations about the requirements as well as precautions to be taken to restart BMS with emphasis on safe delivery and high-quality care.

Background: Initial trials of lung-targeted budesonide (0.25 mg/kg) in surfactant to prevent bronchopulmonary dysplasia (BPD) in premature infants have shown benefit; however, the optimal safe dose is unknown., Methods: Dose-escalation study of budesonide (0.025, 0.05, 0.10 mg/kg) in calfactatant in extremely low gestational age neonates (ELGANs) requiring intubation at 3-14 days. Tracheal aspirate (TA) cytokines, blood budesonide concentrations, and untargeted blood metabolomics were measured. Outcomes were compared with matched infants receiving surfactant in the Trial Of Late SURFactant (TOLSURF)., Results: Twenty-four infants with mean gestational age 25.0 weeks and 743 g birth weight requiring mechanical ventilation were enrolled at mean age 6 days. Budesonide was detected in the blood of all infants with a half-life of 3.4 h. Of 11 infants with elevated TA cytokine levels at baseline, treatment was associated with sustained decrease (mean 65%) at all three dosing levels. There were time- and dose-dependent decreases in blood cortisol concentrations and changes in total blood metabolites. Respiratory outcomes did not differ from the historic controls., Conclusions: Budesonide/surfactant had no clinical respiratory benefit at any dosing levels for intubated ELGANs. One-tenth the dose used in previous trials had minimal systemic metabolic effects and appeared effective for lung-targeted anti-inflammatory action.

Importance: Extremely preterm infants are among the populations receiving the highest levels of transfusions. Erythropoietin has not been recommended for premature infants because most studies have not demonstrated a decrease in donor exposure., Objectives: To determine whether high-dose erythropoietin given within 24 hours of birth through postmenstrual age of 32 completed weeks will decrease the need for blood transfusions., Design, Setting, and Participants: The Preterm Erythropoietin Neuroprotection Trial (PENUT) is a randomized, double-masked clinical trial with participants enrolled at 19 sites consisting of 30 neonatal intensive care units across the United States. Participants were born at a gestational age of 24 weeks (0-6 days) to 27 weeks (6-7 days). Exclusion criteria included conditions known to affect neurodevelopmental outcomes. Of 3266 patients screened, 2325 were excluded, and 941 were enrolled and randomized to erythropoietin (n = 477) or placebo (n = 464). Data were collected from December 12, 2013, to February 25, 2019, and analyzed from March 1 to June 15, 2019., Interventions: In this post hoc analysis, erythropoietin, 1000 U/kg, or placebo was given every 48 hours for 6 doses, followed by 400 U/kg or sham injections 3 times a week through postmenstrual age of 32 weeks., Main Outcomes and Measures: Need for transfusion, transfusion numbers and volume, number of donor exposures, and lowest daily hematocrit level are presented herein., Results: A total of 936 patients (488 male [52.1%]) were included in the analysis, with a mean (SD) gestational age of 25.6 (1.2) weeks and mean (SD) birth weight of 799 (189) g. Erythropoietin treatment (vs placebo) decreased the number of transfusions (unadjusted mean [SD], 3.5 [4.0] vs 5.2 [4.4]), with a relative rate (RR) of 0.66 (95% CI, 0.59-0.75); the cumulative transfused volume (mean [SD], 47.6 [60.4] vs 76.3 [68.2] mL), with a mean difference of -25.7 (95% CI, 18.1-33.3) mL; and donor exposure (mean [SD], 1.6 [1.7] vs 2.4 [2.0]), with an RR of 0.67 (95% CI, 0.58-0.77). Despite fewer transfusions, erythropoietin-treated infants tended to have higher hematocrit levels than placebo-treated infants, most noticeable at gestational week 33 in infants with a gestational age of 27 weeks (mean [SD] hematocrit level in erythropoietin-treated vs placebo-treated cohorts, 36.9% [5.5%] vs 30.4% [4.6%] (P < .001). Of 936 infants, 160 (17.1%) remained transfusion free at the end of 12 postnatal weeks, including 43 in the placebo group and 117 in the erythropoietin group (P < .001)., Conclusions and Relevance: These findings suggest that high-dose erythropoietin as used in the PENUT protocol was effective in reducing transfusion needs in this population of extremely preterm infants., Trial Registration: ClinicalTrials.gov Identifier: NCT01378273.

Bariatric and metabolic surgery are being performed in India for 2 decades. Aim of this paper is to evaluate the changing clinical trends over the last 5 years and to present the other aspects helmed by Obesity and Metabolic Surgery Society of India (OSSI) to aid the growth of research, education, data management and registry, quality control, insurance-related issues and policy change. OSSI conducts an annual survey to collect data pertaining to numbers of surgical procedures. With the approval of the executive committee, data collected from 2014 to 2018 were retrieved and analysed. 20,242 surgical procedures were performed in 2018 which is an 86.7% increase from 2014. Laparoscopic sleeve gastrectomy continued to remain the most popular procedure, it's percent share saw a steady decline from 68 to 48%. One anastomosis gastric bypass showed an unprecedented growth from 14 to 34%. Numbers of laparoscopic Roux en y gastric bypass remained constant at 15-16%. OSSI has also initiated a COE program along with training fellowships and focus on registry and inclusion in insurance coverage. National trends over the past 5 years in bariatric surgery have shown emergence of newer procedures like OAGB, although LSG continues to be the most popular procedure performed These trends give an insight on how the field is evolving and the implications for any distinctive requirements unique to this region These will lay out important directives for not only ensuring good treatment outcomes but also increasing awareness about the disease on the whole.

Objective: To demonstrate the association between the duration of significant patent ductus arteriosus (PDA) and bronchopulmonary dysplasia (BPD) in extremely preterm infants., Methods: All extremely preterm infants (<29 weeks) treated in our Neonatal Intensive Care Unit from January 2013 to March 2016 were included if their PDA status was confirmed at <7 days of life. Infants with genetic syndromes, complex congenital anomalies and insignificant PDAs were excluded. Total duration of significant PDA was estimated by reviewing serial echocardiograms. Significant PDA was diagnosed using our scoring system that was based upon echocardiographic parameters and clinical status of the infants. Study cohort was divided into four groups based on the duration of significant PDA. Group A-No PDA, Group B-PDA <1-week, Group C- PDA 1-2 weeks, and Group D-PDA >2 weeks. ANOVA and multivariate analysis were performed to compare the groups., Results: There were 147 infants with no PDA (Group A), 50, 35, and 41 infants were enrolled in Groups B, C, and D, respectively. There were no differences in maternal and neonatal variables among groups except for the following: maternal smoking, chorioamnionitis, antenatal indomethacin, gestation, birth weight, mode of delivery and incidence of death or BPD. Logistic regression analysis showed that longer duration of significant PDA was associated with higher risk for death or BPD (adjusted OR 1.37, 95% CI 1.03-1.82)., Conclusion: Longer duration of significant PDA is associated with the higher risk for BPD/death in extremely preterm infants.

Introduction: Neonates with hypoxic-ischemic encephalopathy (HIE) undergoing hypothermia may benefit from adjunctive therapy with melatonin. However, melatonin safety, pharmacokinetics (PK), and dosage in this sensitive population are still unknown., Methods and Results: This study assessed the PK and safety of melatonin enteral administration to neonates with HIE undergoing hypothermia. Melatonin was infused at 0.5 mg/kg in five neonates with HIE undergoing hypothermia. Infusion started 1 hour after the neonates reached the target temperature of 33.5°C. Blood samples were collected before and at selective times after melatonin infusion. Abdominal complications or clinically significant changes in patients' vital signs were not found during or after melatonin. The peak plasma concentration reached 0.25 µg/mL. The area under the curve in 24 hours was 4.35 µg/mL*h., Discussion: Melatonin half-life and clearance were prolonged, and the distribution volume decreased compared to adults. In silico simulation estimated that the steady state can be reached after four infusions. Hypothermia does not affect melatonin PK. In humans high blood concentrations with lower doses can be achieved compared to animal experimentation, although intravenous administration is advised in the neonate population. Our study is a preparatory step for future clinical studies aimed at assessing melatonin efficacy in HIE., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Purpose: Quantify short-term outcomes associated with initial surgery [laparotomy (LAP) vs. peritoneal drain (PD)] for necrotizing enterocolitis (NEC) in extremely-low-birth-weight (ELBW) infants., Methods: Using the Children's Hospitals Neonatal Database, we identified ELBW infants <32 weeks' gestation with surgical NEC (sNEC). Unadjusted and multivariable regression analyses were used to estimate the associations between LAP (or PD) and death/short bowel syndrome (SBS) and length of stay (LOS)., Results: LAP was the more common initial procedure for sNEC (n = 359/528, 68%). Infants receiving LAP were older and heavier. Initial procedure was unrelated to death/SBS in both bivariate (LAP: 43% vs PD: 46%, p = 0.573) and multivariable analyses (OR = 0.89, 95% CI = 0.57, 1.38, p = 0.6). LAP was inversely related to mortality (29% vs. 41%, p < 0.007) in bivariate analysis, but not significant in multivariable analysis accounting for markers of preoperative illness severity. However, the association between LAP and SBS (14% vs. 5%, p = 0.012) remained significant in multivariable analyses (adjusted OR = 2.25, p = 0.039). LOS among survivors was unrelated to the first surgical procedure in multivariable analysis., Conclusion: ELBW infants who undergo LAP as the initial operative procedure for sNEC may be at higher risk for SBS without a clear in-hospital survival advantage or shorter hospitalization., Level of Evidence: Level II., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: To study the natural history of postnatal cardiopulmonary adaptation in infants born extremely preterm and establish its association with death or bronchopulmonary dysplasia (BPD)., Study Design: This was a prospective, observational, cohort study of infants born extremely preterm (<29 weeks). Initial echocardiogram was performed at <48 hours of life, followed by serial echocardiograms every 24-48 hours until 14 days of life. Resolution or no resolution of pulmonary hypertension (PH) at 72-96 hours was considered normal or delayed postnatal cardiopulmonary adaptation, respectively. PH between 96 hours and 14 days was defined as subsequent PH. Elevated pulmonary artery pressure throughout the 14 days of life was considered persistent PH. BPD was assessed at 36 weeks of postmenstrual age., Results: Sixty infants were enrolled; 2 died before a sequential echocardiogram could be done at 72-96 hours. Normal and delayed cardiopulmonary adaptation were noted in 26 (45%) and 32 (55%) infants, respectively. Five patterns of postnatal cardiopulmonary adaptation were recognized: normal without subsequent PH (n = 20), normal with subsequent PH (n = 6), delayed adaptation without subsequent PH (n = 6), delayed adaptation with subsequent PH (n = 16), and persistent PH (n = 10). Infants with delayed cardiopulmonary adaptation were of lower gestation and birth weight and required prolonged ventilation and supplemental oxygen (P < .05). On multivariate analysis, the incidence of death or BPD was significantly greater among infants with delayed adaptation (P < .001)., Conclusion: Infants born extremely preterm have normal or delayed postnatal cardiopulmonary adaptation that can be complicated by subsequent or persistent PH. Delayed cardiopulmonary adaptation is associated independently with death or BPD., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Point-of-care (POC) ultrasound refers to the use of portable imaging. Although POC ultrasound is widely available to the neonatologists in Australia and Europe, neonatologists in the United States report limited availability. Our objective was to seek the US neonatologists' perception of barriers and prerequisites in adopting POC ultrasound in neonatal intensive care units. An online survey link was sent via e-mail to 3000 neonatologists included in the database maintained by the American Academy of Pediatrics. Survey results (n = 574) were reported as percentage of total responses. Personal experience requiring an urgent sonography in managing cardiac tamponade or pleural effusion was reported by 78% respondents. However, emergent ultrasound (≤10 min) was not available in 80% of the neonatal intensive care units. We compared the responses based on years of clinical experience (>20 vs <20 years), with 272 (48%) neonatologist reporting more than 20 years of experience. Similarly, results from neonatal fellowship programs were compared with nonteaching/teaching hospitals, with 288 (50%) replies from neonatology fellowship programs. Compared with senior neonatologists, respondents with less than 20 years of clinical experience consider POC ultrasound enhances safety and accuracy of clinical procedures (87% vs 82%) and favor adopting POC ultrasound in clinical practice (92% vs 84%). There were no differences in opinion from neonatology fellowship programs compared with the nonteaching/teaching hospitals. Lack of training guidelines, inadequate support from local radiology department, and legal concerns were reported as the top 3 primary barriers in adopting POC ultrasound. If these barriers could be resolved, 89% respondents were inclined to adopt POC ultrasound in clinical practice.

Objective: To determine the effects of late surfactant on respiratory outcomes determined at 1-year corrected age in the Trial of Late Surfactant (TOLSURF), which randomized newborns of extremely low gestational age (≤28 weeks' gestational age) ventilated at 7-14 days to late surfactant and inhaled nitric oxide vs inhaled nitric oxide-alone (control)., Study Design: Caregivers were surveyed in a double-blinded manner at 3, 6, 9, and 12 months' corrected age to collect information on respiratory resource use (infant medication use, home support, and hospitalization). Infants were classified for composite outcomes of pulmonary morbidity (no PM, determined in infants with no reported respiratory resource use) and persistent PM (determined in infants with any resource use in ≥3 surveys)., Results: Infants (n = 450, late surfactant n = 217, control n = 233) were 25.3 ± 1.2 weeks' gestation and 713 ± 164 g at birth. In the late surfactant group, fewer infants received home respiratory support than in the control group (35.8% vs 52.9%, relative benefit [RB] 1.28 [95% CI 1.07-1.55]). There was no benefit of late surfactant for No PM vs PM (RB 1.27; 95% CI 0.89-1.81) or no persistent PM vs persistent PM (RB 1.01; 95% CI 0.87-1.17). After adjustment for imbalances in baseline characteristics, relative benefit of late surfactant treatment increased: RB 1.40 (95% CI 0.89-1.80) for no PM and RB 1.24 (95% CI 1.08-1.42) for no persistent PM., Conclusion: Treatment of newborns of extremely low gestational age with late surfactant in combination with inhaled nitric oxide decreased use of home respiratory support and may decrease persistent pulmonary morbidity., Trial Registration: ClinicalTrials.gov: NCT01022580., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objective: To assess whether late surfactant treatment in extremely low gestational age (GA) newborn infants requiring ventilation at 7-14 days, who often have surfactant deficiency and dysfunction, safely improves survival without bronchopulmonary dysplasia (BPD)., Study Design: Extremely low GA newborn infants (GA ≤28 0/7 weeks) who required mechanical ventilation at 7-14 days were enrolled in a randomized, masked controlled trial at 25 US centers. All infants received inhaled nitric oxide and either surfactant (calfactant/Infasurf) or sham instillation every 1-3 days to a maximum of 5 doses while intubated. The primary outcome was survival at 36 weeks postmenstrual age (PMA) without BPD, as evaluated by physiological oxygen/flow reduction., Results: A total of 511 infants were enrolled between January 2010 and September 2013. There were no differences between the treated and control groups in mean birth weight (701 ± 164 g), GA (25.2 ± 1.2 weeks), percentage born at GA <26 weeks (70.6%), race, sex, severity of lung disease at enrollment, or comorbidities of prematurity. Survival without BPD did not differ between the treated and control groups at 36 weeks PMA (31.3% vs 31.7%; relative benefit, 0.98; 95% CI, 0.75-1.28; P = .89) or 40 weeks PMA (58.7% vs 54.1%; relative benefit, 1.08; 95% CI, 0.92-1.27; P = .33). There were no between-group differences in serious adverse events, comorbidities of prematurity, or severity of lung disease to 36 weeks., Conclusion: Late treatment with up to 5 doses of surfactant in ventilated premature infants receiving inhaled nitric oxide was well tolerated, but did not improve survival without BPD at 36 or 40 weeks. Pulmonary and neurodevelopmental assessments are ongoing., Trial Registration: ClinicalTrials.gov: NCT01022580., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objective: This study aims to determine predischarge palivizumab receipt prevalence among infants ≤ 36 weeks' gestational age., Study Design: This retrospective cohort study used hospital discharge records from the Premier Perspective database (Premier Inc., Charlotte, NC) of infants ≤ 36 weeks' gestational age who were discharged home after birth hospitalization during the November-March respiratory syncytial virus (RSV) seasons from 2006 to 2011. Descriptive statistics were performed and logistic regression was employed to identify differences in categorical variables., Results: Among infants ≤ 36 weeks' gestational age discharged home during the RSV seasons, 21.4 to 27.0% had a record of palivizumab receipt before discharge. Among infants ≤ 30 weeks' gestational age, palivizumab receipt was 82.3 to 88.8%. Receipt varied considerably at the hospital level, from 0 to 100%., Conclusion: This study improves our understanding of characteristics associated with predischarge palivizumab administration. The identified gaps in recommended care can help inform future implementation of palivizumab and other interventions to help improve the health of high-risk preterm infants in the United States., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Kidney transplant patients (KTPs) have a potential tendency to develop oral lesions due to the administration of immunosuppressive drugs, but their prevalence is still obscure. The aim of the present study was to investigate the oral clinical findings in a group of renal transplant patients in comparison with ageand sex-matched healthy controls (HCs). Three hundred KTPs who underwent transplantation at least six months earlier and 296 HCs were examined clinically for the presence of any oral lesions. Demographic and additional details regarding medications, systemic diseases and duration after transplantation were recorded. Statistical analysis was performed using the Chi-square test, with significance set at P <0.05. The prevalence of oral lesions in KTPs was 56.8% as compared with 29.7% in HCs. The most common lesion observed in KTPs was gingival overgrowth (21.8%), followed by candidiasis (17.1%). Coated tongue (15.9%), followed by leukoplakia (11.3%), were common in HCs. Both gingival hyperplasia and coated tongue were significantly related to poor oral hygiene (P <0.05), but were not significantly related to the immunosuppressive therapy (P >0.05). The findings of the present study indicate the need for a routine and regular oral health check-up, with emphasis on maintenance of oral hygiene for renal transplant patients.

Nocebo effect, originally denoting the negative counterpart of the placebo phenomenon, is now better defined as the occurrence of adverse effects to a therapeutic intervention because the patient expects them to develop. More commonly encountered in patients with a past negative experience, this effect stems from highly active processes in the central nervous system, mediated by specific neurotransmitters and modulated by psychological mechanisms such as expectation and conditioning. The magnitude of nocebo effect in clinical medicine is being increasingly appreciated and its relevance encompasses clinical trials as well as clinical practice. Although there is hardly any reference to the term nocebo in dermatology articles, the phenomenon is encountered routinely by dermatologists. Dermatology patients are more susceptible to nocebo responses owing to the psychological concern from visibility of skin lesions and the chronicity, unpredictable course, lack of 'permanent cure' and frequent relapses of skin disorders. While finasteride remains the prototypical drug that displays a prominent nocebo effect in dermatologic therapeutics, other drugs such as isotretinoin are also likely inducers. This peculiar phenomenon has recently been appreciated in the modulation of itch perception and in controlled drug provocation tests in patients with a history of adverse drug reactions. Considering the conflict between patients' right to information about treatment related adverse effects and the likelihood of nocebo effect stemming from information disclosure, the prospect of ethically minimizing nocebo effect remains daunting. In this article, we review the concept of nocebo effect, its postulated mechanism, relevance in clinical dermatology and techniques to prevent it from becoming a barrier to effective patient management.

Background/purpose: The optimal surgical approach in infants with gastroschisis (GS) is unknown. The purpose of this study was to estimate the association between staged closure and length of stay (LOS) in infants with GS., Design/methods: We used the Children's Hospital Neonatal Database to identify surviving infants with GS born ≥34 weeks' gestation referred to participating NICUs. Infants with complex GS, bowel atresia, or referred after 2 days of age were excluded. The primary outcome was LOS; multivariable linear regression was used to quantify the relationship between staged closure and LOS., Results: Among 442 eligible infants, staged closure occurred in 68.1% and was associated with an increased median LOS relative to odds ration (OR):primary closure (37 vs. 28 days, p<0.001). This association persisted in the multivariable equation (β=1.35, 95% CI: 1.21, 1.52, p<0.001) after adjusting for the presence of necrotizing enterocolitis, short bowel syndrome, and central-line associated bloodstream infections., Conclusions: In this large, multicenter cohort of infants with GS, staged closure was independently associated with increased LOS. These data can be used to enhance antenatal and pre-operative counseling and also suggest that some infants who receive staged closure may benefit from primary repair., (Copyright © 2014 Elsevier Inc. All rights reserved.)